Bronchial asthma is considered to be a multifactorial disease. In other words, bronchial asthma is caused by the interaction of many different genes, each of which is influenced by various environmental factors. Thus, it has been extremely difficult to identify a specific gene which causes bronchial asthma.
Currently, bronchial asthma is categorized as a chronic inflammatory disease of the respiratory tract. It has been pointed out that allergic reactions at the respiratory tract mucosa and bronchial smooth muscle is closely involved in pathologic formation of bronchial asthma. Therefore, understanding the condition of allergic reactions in these tissues is an important issue in diagnosis of bronchial asthma. In addition, control of allergic reactions is an issue in treatment of bronchial asthma.
On the other hand, the expression of mutated or defective genes, or overexpression or reduction of the expression of specific gene is thought to be involved in allergic diseases. To elucidate the role of gene expression in diseases, it is necessary to understand how a gene is involved in triggering disease onset and how expression of the gene is altered by external stimulants such as drugs.
Incidentally, atopic diathesis that is accompanied by hyperproduction of IgE antibodies is seen in many bronchial asthma patients. Many causes are considered for bronchial asthma, but there is no doubt that atopic diathesis is a cause of hypersensitivity in many patients. It has been predicted that the mechanism of respiratory tract occlusion in asthmatic attack is contraction of the bronchial smooth muscle, or edema and respiratory tract endocrine enhancement of the respiratory tract mucosa. I-type allergic reaction in the respiratory tract due to exposure to pathogenic allergen has an important role in such changes in the respiratory tract.
In recent years, IL-4 and IL-13 have been suggested to have important roles in the onset of bronchial asthma. Therefore, for example, in the respiratory tract epithelial cells and bronchial smooth muscles, genes that change their expression level due to IL-4 and IL-13 are thought to be related to bronchial asthma. However, based on such concept, there have been no reports on isolation of genes that specifically change their expression level due to IL-4 and IL-13.
In recent diagnosis of allergic diseases, history taking, and confirmation of the patient's family history and own anamnesis are important factors in general. In addition, for diagnosis of allergy based on more objective information, a test method using patient's blood sample and method for observing patient's immune response to allergen are also performed. Examples of the former method are the allergen-specific IgE measurement, leukocyte histamine release test, lymphocyte stimulating test, or the like. Presence of an allergen-specific IgE is a proof for the allergic reaction to that allergen. However, in some patients, allergen-specific IgE may not necessarily be detected. Furthermore, the assay principle of IgE requires performing tests for all of the allergens necessary for diagnosis. Leukocyte histamine release test and lymphocyte stimulating test are the methods for observing the immune system reaction toward a specific allergen in vitro. These methods are complicate in operation.
On the other hand, another method is also known, wherein the immune response observed when a patient is actually contacted with an allergen is used for diagnosing an allergy (latter method). Such a test includes the prick test, scratch test, patch test, intradermal reaction, or induction test. Indeed these tests allow the direct diagnosis of patient's allergic reaction but they can be said to be highly invasive tests wherein patients are actually exposed to allergen.
In addition, regardless of the allergen types, test methods for proving the involvement of allergic reaction are also attempted. For example, a high serum IgE titer may indicate the occurrence of allergic reaction in the patient. The serum IgE titer is information corresponding to the total amount of allergen-specific IgE. Though it is easy to determine the total amount of IgE regardless of the type of allergen, IgE titer may be reduced in some patients with a non-atopic bronchitis or the like.
Therefore, a marker (indicator) for an allergic disease that is not only less risky to patients but also capable of readily providing information necessary for diagnosis would be useful.
Particularly, bronchial asthmatic attack due to allergic reaction markedly inhibits patient's respiration, and, in severe cases, it may bring about death due to respiratory insufficiency. Therefore, prompt identification of the cause, and appropriate treatment must be given to patients affected with bronchial asthmatic attack. However, there are no reports on genes found to have a relation to bronchial asthmatic attack.
Regardless of the presence or absence of an attack, there are many reports on attempts to isolate genes relating to patients with allergic diseases. Genes that can be isolated by such an approach can be said to be genes relating to allergic diathesis. In contrast, genes relating to the attack can be expected to be useful as an indicator for diagnosis of the attack and for treatment of attacks needing greatly urgent clinical treatment.